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Hair Follicle Regeneration pp 277–290Cite as

Wound Healing Induced Hair Follicle Regeneration

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Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL,volume 72))

Abstract

Introduction Adult mammals possess very limited regeneration potential. Wound-induced hair neogenesis (WIHN) is a rare regenerative event observed in mammals, in which de novo hair follicles are formed at the wound site. The phenomenon has been observed more than half a century ago, yet the mechanism remains unclear. Recently, more mechanistic studies have shed light onto the complex cellular signaling and mechanical events during WIHN. Interestingly, many of the mechanisms in WIHN are shared with those found in embryonic hair follicle development. Here we review emerging works regarding WIHN mechanisms and potential clinical applications for hair follicle regeneration and improved wound healing outcomes. Methods For the selection of literature covered in this chapter we used Pubmed database. We used keywords such as wound-induced hair follicle neogenesis, embryonic hair follicle development, scarless regeneration, Wnt signaling, Hedgehog signaling. Results Hair follicles generated in WIHN are formed from non-hair-residing epithelial and dermal cells. Extrinsic signals such as Wnt and Shh shown to promote embryonic hair follicle formation are also crucial players in WIHN. Understanding WIHN mechanisms provides a basis to achieve regenerative wound healing with appendage formation. Conclusions Although there has been much progress in identifying the critical factors that promote adult hair follicle neogenesis, there is a great need for exploring the different cellular behavior and signaling mechanisms involved in WIHN and how they can be applied clinically.

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References

  1. Breedis C (1954) Regeneration of hair follicles and sebaceous glands from the epithelium of scars in the rabbit. Cancer Res 14(8):575–579

    CAS  PubMed  Google Scholar 

  2. Billingham RE, Russell PS (1956) Incomplete wound contracture and the phenomenon of hair neogenesis in rabbits’ skin. Nature 177(4513):791–792

    Article  CAS  Google Scholar 

  3. Kligman AM, Strauss JS (1956) The formation of vellus hair follicles from human adult epidermis. J Invest Dermatol 27(1):19–23

    Article  CAS  Google Scholar 

  4. Ito M, Yang Z, Andl T, Cui C, Kim N, Millar SE et al (2007) Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447(7142):316–320

    Article  CAS  Google Scholar 

  5. Lim CH, Sun Q, Ratti K, Lee S-H, Zheng Y, Takeo M et al (2018) Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing. Nat Commun 9(1):4903

    Article  Google Scholar 

  6. Harn H, Wang S, Lai Y, Van Handel B, Liang Y, Tsai S et al (2021) 609 Symmetry breaking of tissue mechanics in wound induced hair follicle regeneration. J Invest Dermatol 141(5):S106

    Article  Google Scholar 

  7. Wong T-W, Hughes M, Wang S-H (2018) Never too old to regenerate? Wound induced hair follicle neogenesis after secondary intention healing in a geriatric patient. J Tissue Viability 27(2):114–116

    Article  Google Scholar 

  8. Park S, Gonzalez DG, Guirao B, Boucher JD, Cockburn K, Marsh ED et al (2017) Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice. Nat Cell Biol 19(3):155–163

    Article  CAS  Google Scholar 

  9. Aragona M, Dekoninck S, Rulands S, Lenglez S, Mascré G, Simons BD et al (2017) Defining stem cell dynamics and migration during wound healing in mouse skin epidermis. Nat Commun 8:14684

    Article  Google Scholar 

  10. Sun BK, Siprashvili Z, Khavari PA (2014) Advances in skin grafting and treatment of cutaneous wounds. Science 346(6212):941–945

    Article  CAS  Google Scholar 

  11. Yang R, Liu F, Wang J, Chen X, Xie J, Xiong K (2019) Epidermal stem cells in wound healing and their clinical applications. Stem Cell Res Ther 10(1):229

    Article  Google Scholar 

  12. Walmsley GG, Maan ZN, Wong VW, Duscher D, Hu MS, Zielins ER et al (2015) Scarless wound healing: chasing the holy grail. Plast Reconstr Surg 135(3):907–917

    Article  CAS  Google Scholar 

  13. Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U (2017) Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res 58(1–2):81–94

    Article  Google Scholar 

  14. Cotsarelis G, Sun TT, Lavker RM (1990) Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61(7):1329–1337

    Article  CAS  Google Scholar 

  15. Liu Y, Lyle S, Yang Z, Cotsarelis G (2003) Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. J Invest Dermatol 121(5):963–968

    Article  CAS  Google Scholar 

  16. Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N et al (2010) Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 327(5971):1385–1389

    Article  CAS  Google Scholar 

  17. Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453(7193):314–321

    Article  CAS  Google Scholar 

  18. Driskell RR, Lichtenberger BM, Hoste E, Kretzschmar K, Simons BD, Charalambous M et al (2013) Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature 504(7479):277–281

    Article  CAS  Google Scholar 

  19. Abbasi S, Sinha S, Labit E, Rosin NL, Yoon G, Rahmani W et al (2020) Distinct regulatory programs control the latent regenerative potential of dermal fibroblasts during wound healing. Cell Stem Cell 27(3):396-412.e6

    Article  CAS  Google Scholar 

  20. Millar SE (2002) Molecular mechanisms regulating hair follicle development. J Invest Dermatol 118(2):216–225

    Article  CAS  Google Scholar 

  21. Myung PS, Takeo M, Ito M, Atit RP (2013) Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration. J Invest Dermatol 133(1):31–41

    Article  CAS  Google Scholar 

  22. Gay D, Kwon O, Zhang Z, Spata M, Plikus MV, Holler PD et al (2013) Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding. Nat Med 19(7):916–923

    Article  CAS  Google Scholar 

  23. Chiang C, Swan RZ, Grachtchouk M, Bolinger M, Litingtung Y, Robertson EK et al (1999) Essential role for Sonic hedgehog during hair follicle morphogenesis. Dev Biol 205(1):1–9

    Article  CAS  Google Scholar 

  24. St-Jacques B, Dassule HR, Karavanova I, Botchkarev VA, Li J, Danielian PS et al (1998) Sonic hedgehog signaling is essential for hair development. Curr Biol 8(19):1058–1068

    Article  CAS  Google Scholar 

  25. Sennett R, Rendl M (2012) Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling. Semin Cell Dev Biol 23(8):917–927

    Article  CAS  Google Scholar 

  26. Woo W-M, Zhen HH, Oro AE (2012) Shh maintains dermal papilla identity and hair morphogenesis via a Noggin-Shh regulatory loop. Genes Dev 26(11):1235–1246

    Article  CAS  Google Scholar 

  27. Ouspenskaia T, Matos I, Mertz AF, Fiore VF, Fuchs E (2016) WNT-SHH antagonism specifies and expands stem cells prior to niche formation. Cell 164(1–2):156–169

    Article  CAS  Google Scholar 

  28. Wang N, Wu Y, Zeng N, Wang H, Deng P, Xu Y, et al (2016) E2F1 hinders skin wound healing by repressing vascular endothelial growth factor (VEGF) expression, neovascularization, and macrophage recruitment. PLoS One 11(8):e0160411

    Google Scholar 

  29. Nelson AM, Loy DE, Lawson JA, Katseff AS, Fitzgerald GA, Garza LA (2013) Prostaglandin D2 inhibits wound-induced hair follicle neogenesis through the receptor, Gpr44. J Invest Dermatol 133(4):881–889

    Article  CAS  Google Scholar 

  30. Fu J, Hsu W (2013) Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis. J Invest Dermatol 133(4):890–898

    Article  CAS  Google Scholar 

  31. Cohen J (1961) The transplantation of individual rat and guineapig whisker papillae. J Embryol Exp Morphol 9:117–127

    CAS  PubMed  Google Scholar 

  32. Hughes MW, Jiang T-X, Plikus MV, Guerrero-Juarez CF, Lin C-H, Schafer C et al (2018) Msx2 supports epidermal competency during wound-induced hair follicle neogenesis. J Invest Dermatol 138(9):2041–2050

    Article  CAS  Google Scholar 

  33. Gat U, DasGupta R, Degenstein L, Fuchs E (1998) De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated β-catenin in skin. Cell 95(5):605–614

    Article  CAS  Google Scholar 

  34. Sun X, Are A, Annusver K, Sivan U, Jacob T, Dalessandri T, et al (2020) Coordinated hedgehog signaling induces new hair follicles in adult skin. Elife [Internet]. http://dx.doi.org/https://doi.org/10.7554/eLife.46756

  35. Shah M, Foreman DM, Ferguson MW (1995) Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. J Cell Sci 108(Pt 3):985–1002

    Article  CAS  Google Scholar 

  36. Lorenz HP, Lin RY, Longaker MT, Whitby DJ, Adzick NS (1995) The fetal fibroblast: The effector cell of scarless fetal skin repair. Plast Reconstr Surg 96(6):1251–1259

    Article  CAS  Google Scholar 

  37. Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S et al (2005) Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 115(1):56–65

    Article  CAS  Google Scholar 

  38. Kasuya A, Ito T, Tokura Y (2018) M2 macrophages promote wound-induced hair neogenesis. J Dermatol Sci [Internet]. http://dx.doi.org/https://doi.org/10.1016/j.jdermsci.2018.05.004

  39. Gay D, Ghinatti G, Guerrero-Juarez CF, Ferrer RA, Ferri F, Lim CH, et al (2020) Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing. Sci Adv 6(12):eaay3704

    Google Scholar 

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Acknowledgements

We’d like to thank Dr. Mayumi Ito, Dr. Denise Gay and Dr. Chae Ho Lim for their helpful feedback on the manuscript.

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Authors and Affiliations

  1. Departments of Dermatology and Pathology, Yale University, New Haven, CT, USA

    Yiqun Jiang

  2. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA

    Peggy Myung

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  1. Yiqun Jiang
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Correspondence to Peggy Myung .

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Editors and Affiliations

  1. Mediteknia Dermatology and Hair Transplant Clinic, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain

    Francisco Jimenez

  2. Department of Bioengineering, Imperial College London, London, UK

    Claire Higgins

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Jiang, Y., Myung, P. (2022). Wound Healing Induced Hair Follicle Regeneration. In: Jimenez, F., Higgins, C. (eds) Hair Follicle Regeneration. Stem Cell Biology and Regenerative Medicine, vol 72. Humana, Cham. https://doi.org/10.1007/978-3-030-98331-4_13

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